Chemical reprogramming to generate neuronal cells

Abstract

Compositions and methods are described herein for chemically inducing cells to change their differentiation state and become neuronal cells.

What is claimed: 
     
       1. A method of generating a neuronal cell or a neuronal progenitor cell, comprising contacting a selected differentiated, non-neuronal cell with a composition comprising active agents CHIR99021; LDN193189; A83-01; Hh-Agl.5; retinoic acid; SMER28; RG108, parnate, and bFGF, in an amount sufficient to reprogram the selected cell to thereby generate a neuronal progenitor cell. 
     
     
       2. The method of  claim 1 , wherein the selected cell contacted with the composition is a somatic cell, a population of cells, a heterogeneous mixture of cells, a population of non-neuronal cells, or a combination thereof. 
     
     
       3. The method of  claim 1 , wherein the selected cell is a newborn cord blood cell. 
     
     
       4. The method of  claim 1 , wherein the selected cell is an allogenic or autologous cell. 
     
     
       5. The method of  claim 1 , wherein the agents are present in an amount sufficient to induce the selected cell to express Pax6, Sox2, Ascl1, Olig2, Nestin, Tuj1, Tau, NeuN, MAP2, synapsin, Sytl, Syt4, Sytl3, Syt16, NeuroD, Is1l, cholineacetyltransferase, or any combination thereof. 
     
     
       6. The method of  claim 1 , further comprising administering the neuronal cell, the neuronal progenitor cell, or a combination thereof to a subject. 
     
     
       7. The method of  claim 6 , wherein the subject suffers or is suspected of suffering from Amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, multiple sclerosis, Primary lateral sclerosis (PLS), Progressive bulbar palsy, Pseudobulbar palsy, Primary lateral sclerosis (PLS), Progressive muscular atrophy, Spinal muscular atrophy (SMA), including Type I (also called Werdnig-Hoffmann disease), Type II, Type III (Kugelberg-Welander disease), Fazio-Londe disease, Huntington's disease, Kennedy's disease also known as progressive spinobulbar muscular atrophy, hereditary spastic paraplegia (HSP), congenital SMA with arthrogryposis, Post-polio syndrome (PPS), traumatic spinal cord injury, progressive pseudobulbar palsy, progressive muscular atrophy, stroke, head trauma, spinal cord injury, or a combination thereof.